Tumor Necrosis Factor‐α Modulates Survival, Proliferation, and Neuronal Differentiation in Neonatal Subventricular Zone Cell Cultures

摘要: Tumor necrosis factor (TNF)-alpha has been reported to modulate brain injury, but remarkably, little is known about its effects on neurogenesis. We report that TNF-alpha strongly influences survival, proliferation, and neuronal differentiation in cultured subventricular zone (SVZ) neural stem/progenitor cells derived from the neonatal P1-3 C57BL/6 mice. By using single-cell calcium imaging, we developed a method, based cellular response KCl and/or histamine, allows functional evaluation of differentiation. Exposure SVZ cultures 1 10 ng/ml mouse or human recombinant resulted increased displaying neuronal-like profile [Ca2+](i) responses, compared with predominant immature observed control, nontreated cultures. Moreover, by neutralizing antibodies for each receptor, found proneurogenic effect mediated via tumor receptor activation. Accordingly, percentage nuclear protein-positive neurons was following exposure TNF-alpha. Interestingly, induced cell whereas 100 apoptotic death. 15 minutes 6 hours caused an increase phospho-stress-activated protein kinase/c-Jun N-terminal kinase immunoreactivity initially nucleus then growing axons, colocalizing tau, consistent axonogenesis. Taken together, these results show induces neurogenesis TNF-alpha, proinflammatory cytokine factor, may play central role promoting repair injury infection.